Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2018
Artificial intelligence-derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00216385 (A Randomised Open-Label Controlled Trial of a 4-Month Gatifloxacin-Containing Regimen Versus Standard Regimen for the Treatment of Adult Patients With Pulmonary Tuberculosis), which is not on this map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomised Open-Label Controlled Trial of a 4-Month Gatifloxacin-Containing Regimen Versus Standard Regimen for the Treatment of Adult Patients With Pulmonary Tuberculosis
Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Preclinical pharmacokinetics/pharmacodynamics studies defining the role of ethambutol inAntimicrobial agents and chemotherapy · 2026Article
- Determining the Delamanid Pharmacokinetics/Pharmacodynamics Susceptibility Breakpoint Using Monte Carlo Experiments.Antimicrobial agents and chemotherapy · 2023Article
- Dynamic PET-facilitated modeling and high-dose rifampin regimens forScience translational medicine · 2021Article
- Comparative Effectiveness of Methotrexate versus Methylprednisolone in Treatment Naïve Pulmonary Sarcoidosis Patients.Diagnostics (Basel, Switzerland) · 2021Article
- Visualizing the dynamics of tuberculosis pathology using molecular imaging.The Journal of clinical investigation · 2021Review
- Repurposing Cefazolin-Avibactam for the Treatment of Drug ResistantFrontiers in pharmacology · 2021Article
- Machine learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis.BMC infectious diseases · 2020Article
- Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Dynamic imaging in patients with tuberculosis reveals heterogeneous drug exposures in pulmonary lesions.Nature medicine · 2020Article
- Quantitative assessment of the activity of antituberculosis drugs and regimens.Expert review of anti-infective therapy · 2019Review
- Pharmacokinetic/Pharmacodynamic Background and Methods and Scientific Evidence Base for Dosing of Second-line Tuberculosis Drugs.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet!Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Transformation Morphisms and Time-to-Extinction Analysis That Map Therapy Duration From Preclinical Models to Patients With Tuberculosis: Translating From Apples to Oranges.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- The Role of Novel Approaches and New Findings in the Pharmacology of Tuberculosis Medicines in Improving Treatment Outcomes.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
Background: In the experimental arm of the OFLOTUB trial, gatifloxacin replaced ethambutol in the standard 4-month regimen for drug-susceptible pulmonary tuberculosis. The study included a nested pharmacokinetic (PK) study. We sought to determine if PK variability played a role in patient outcomes. Methods: Patients recruited in the trial were followed for 24 months, and relapse ascertained using spoligotyping. Blood was drawn for drug concentrations on 2 separate days during the first 2 months of therapy, and compartmental PK analyses was performed. Failure to attain sustained sputum culture conversion at the end of treatment, relapse, or death during follow-up defined therapy failure. In addition to standard statistical analyses, we utilized an ensemble of machine-learning methods to identify patterns and predictors of therapy failure from among 27 clinical and laboratory features. Results: Of 126 patients, 95 (75%) had favorable outcomes and 19 (15%) failed therapy, relapsed, or died. Pyrazinamide and rifampicin peak concentrations and area under the concentration-time curves (AUCs) were ranked higher (more important) than gatifloxacin AUCs. The distribution of individual drug concentrations and their ranking varied significantly between South African and West African trial sites; however, drug concentrations still accounted for 31% and 75% of variance of outcomes, respectively. We identified a 3-way antagonistic interaction of pyrazinamide, gatifloxacin, and rifampicin concentrations. These negative interactions disappeared if rifampicin peak concentration was above 7 mg/L. Conclusions: Concentration-dependent antagonism contributed to death, relapse, and therapy failure but was abrogated by high rifampicin concentrations. Therefore, increasing both rifampin and gatifloxacin doses could improve outcomes. Clinical Trials Registration: NCT00216385.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.